Diagnostic exome sequencing in 50 patients with high myopia

Abstract

Purpose : High myopia (≤-6 diopters) represents a significant public health issue. The development of potential treatments make the understanding of the genetic etiology very important. High myopia is a heterogeneous condition, and without clear accompanying features it can be difficult to pinpoint a genetic cause. The aim of this study was to evaluate the diagnostic yield of whole exome sequencing (WES) in patients with high myopia.

Methods : Patients with high myopia were recruited by ophthalmologists and clinical geneticists. Clinical features were categorized into isolated high myopia, high myopia with other ocular features or syndromic high myopia with systemic involvement. WES was performed using a gene panel including 477 genes involved in inherited eye disorders.

Results : WES was performed in 50 patients with high myopia; the majority had isolated high myopia (64%). A genetic cause was identified in 11 patients (22%; mean age at diagnosis 9.4 years (SD 7.5); mean refractive error -12.60 diopters (SD 6.22)). Four patients had mutations in known retinal dystrophy genes (GUCY2D; FAM161A; PDE6H; CACNA1F); 3 female patients had a ARR3 mutation (X-linked female limited high myopia); 2 patients had homozygous or compound heterozygous COL18A1 mutations (Knobloch syndrome); 1 patient had a COL2A1 mutation (Stickler syndrome); 1 patient had a PAX6 mutation. In 14 patients (28%) a variant of unknown significance was found; further segregation or follow-up examinations are necessary.

Conclusions : The diagnostic yield of our WES vision gene panel for high myopia was 22%. It enabled us to diagnose various causes of high myopia, i.e. retinal dystrophies, connective tissue diseases, and non-syndromic high myopia, allowing appropriate follow up of systemic and ocular features and genetic counseling.

This is a 2020 ARVO Annual Meeting abstract.